Title

Author

Degree Type

Thesis

Date of Award

2017

Degree Name

Master of Science

Department

Biomedical Sciences

Major

Neuroscience

First Advisor

Nicholas D. Jeffery

Second Advisor

Jeffrey Trimarchi

Abstract

Proprioception, the sense of position and movement of parts of the body is crucial for proper motor control, and its disruption is associated with various pathologies, particularly joint or muscle injury. While there have been studies into the functional changes of proprioception after injury, the underlying cellular and molecular mechanisms underlying this phenomenon are mostly unknown. Pain hypersensitivity following tissue or nerve damage is a possible analog to proprioceptive disruption. Inflammatory and damage-induced pain have been linked to activation of specific signaling pathways as well as the upregulation of various proteins. We set out to elucidate any parallel between injury-associated pain and proprioceptive disruption at the level of the spinal cord and dorsal root ganglia (DRGs). First, we analyzed global gene expression in dorsal root ganglia (DRGs) in a rat model of anterior cruciate ligament (ACL) injury, a condition commonly associated with altered proprioception. Subsequently, we sought to develop a protocol for targeting specific cells in the muscle proprioceptive circuitry, including DRG neurons and gamma motoneurons (γ-MNs) by combining DiI retrograde axonal tracing with single-cell RNA isolation. Preliminary results suggest an upregulation of matrix metalloproteinase 9 (MMP-9) and neurotrophin-4 (NTF-4) in DRG innervating lesioned knees in rats, suggesting neuropathic pain development, but no significant changes were found in any genes specific to proprioceptive afferents. DiI traced to the correct DRG and spinal cord regions, and a dissociated cell produced an adequate quantity of cDNA. The muscle tracing protocol provides a useful tool for further investigating proprioceptive alterations, the potential to modify the protocol for knee injections may further our understanding of complications in recovery from ACL injuries.